Pathology Clinical Cases

Question 1

List the T subcategories for TNM staging of colorectal cancer.

Answer 1

• TX: Primary tumour cannot be assessed.
• T0: No evidence of primary tumour.
• T1: Tumour invades submucosa.
• T2: Tumour invades muscularis propria.
• T3: Tumour invades subserosa or non-peritonealised tissues.
• T4: Tumour perforates visceral peritoneum and / or directly invades other organs.
• If the tumour is present in the mucosa but does not invade the submucosa, it is a dysplasia (not a cancer).

Question 2

List the N subcategories for TNM staging of colorectal cancer.

Answer 2

• NX: Regional lymph nodes cannot be assessed.
• N0: No regional lymph node metastatic disease.
• N1: Metastatic disease in 1-3 regional lymph nodes.
• N3: Metastatic disease in 4 or more lymph nodes.

Question 3

List the M subcategories for TNM staging of colorectal cancer.

Answer 3

• MX: Metastasis cannot be measured.
• M0: Cancer has not spread to other parts of the body.
• M1: Cancer has spread to other parts of the body.

Question 4

List the subtypes of colorectal adenocarcinomas.

Which subtype represents the majority of colorectal adenocarcinomas?

Answer 4

Colorectal adenocarcinomas are either:

1 - Microsatellite stable.

2 - Microsatellite instable.

• The majority (80%) are microsatellite stable.

Question 5

Why might the presence microsatellite instabilities imply that there is further genetic damage?

Answer 5

• Microsatellites are usually corrected by DNA mismatch repair.
• If DNA mismatch repair is impaired, the microsatellites will remain.
• Therefore, the presence of microsatellite instabilities implies that there is a defect in the cell’s DNA repair mechanisms.

Question 6

List 4 implications of microsatellite instability.

Answer 6

1 - Aneuploidy.

2 - Amplifications.

3 - Translocations.

4 - Mutations of genes controlling cell growth.

Question 7

List 4 characteristics of highly microsatellite instable (MSI-H) tumours.

Answer 7

MSI-H tumours are:

1 - Proximal, with a well-defined border.

2 - Poorly differentiated.

3 - Mucinous when examined histologically.

4 - More likely to show lymphocytic infiltration.

Question 8

Give an example of a disease that predisposes patients to highly microsatellite instable (MSI-H) tumours.

Answer 8

Hereditary non-polyposis colorectal cancer (Lynch syndrome) predisposes patients to highly microsatellite instable (MSI-H) tumours.

Question 9

What inheritance pattern does HNPCC / Lynch syndrome show?

Answer 9

HNPCC / Lynch syndrome is an autosomal dominant disorder.

Question 10

Which genes are affected in HNPCC / Lynch syndrome?

Answer 10

• Mismatch repair (MMR) genes are affected in HNPCC / Lynch syndrome. Examples include:

1 - MSH2.

2 - MSH6.

3 - MLH1.

Question 11

In what proportion of colorectal tumours are RAS mutations present?

Why is this important clinically?

Answer 11

• RAS mutations are present in ~1/2 of all colorectal tumours.
• Patients with tumours that have mutations in RAS are unlikely to benefit from anti-epidermal growth factor receptor (anti-EGFR) antibodies (because the MAPK pathway is dysfunctional).

Question 12

In what proportion of colorectal cancers are BRAF mutations present?

Why is this important clinically?

Answer 12

• BRAF mutations are present in 8% of all colorectal tumours.
• Patients with tumours that have mutations in BRAF usually have a poor prognosis (but for some reason it isn’t a negative marker for anti-EGFR therapy).

Question 13

List the 2 subtypes of inflammatory bowel disease (IBD).

Answer 13

IBD includes:

1 - Crohn’s disease.

2 - Ulcerative colitis.

Question 14

What is the primary difference between the distribution of affected lower GI tissue in Crohn’s disease and ulcerative colitis?

Answer 14

• In Crohn’s disease, it is usually the ileocaecal junction that is affected, but it can also occur in patches across the whole lower GI tract.
• In ulcerative colitis, it is usually the distal colon and rectum that are affected.